End stage renal disease (ESRD) affects over 425,000 Americans and continues to increase in prevalence at 8% annually. Kidney transplant, the treatment of choice, is severely limited by scarcity of donor organs such that only 25% on the waiting list for a transplant survive long enough to receive a kidney. The alternative treatment for over 300,000 ESRD patients is dialysis, which is expensive, inconvenient, and confers significant morbidity and mortality. This Quantum Project will ultimately deliver an implantable, self-regulating, bioartificial kidney that will eliminate majority of the >50 million dialysis procedures performed annually in the US. The extracorporeal Renal Assist Device (RAD), which is in Phase II clinical trials, is a large bioartificial kidney that combines hemofiltration with proximal tubule cell therapy to mimic many of the metabolic, endocrine, and immunological functions of a healthy kidney. However, successful adoption of the RAD for routine treatment of ESRD patients will be hampered by its large overall size, complex assembly, and labor-intensive application. This Quantum Project will apply MEMS (microelectromechanical systems) technology and compatible nanotechnology strategies to miniaturize the RAD into a compact, implantable, self-monitoring and self-regulating bioartificial kidney. The miniaturized implantable RAD will: (1) eliminate disposables and dialysate by coupling a durable, long-life hemofilter with a bioreactor of renal tubule cells, exactly as happens in the kidney;and (2) self-regulate extracellular fluid volume and clearance through integrated MEMS sensors, control electronics, and actuators. Phase I of the Quantum Project will establish the final operational parameters for the hemofilter and the tubule cell bioreactor. For the hemofilter, the optimum pore size for membrane permselectivity, pore layout for mechanical strength and robustness, and surface coatings for blood biocompatibility will be established. For the cell bioreactor, culture conditions for maximum tubule cell transport will be determined. Phase I will culminate in an animal demonstration of balanced filtration and re-absorption by a single proximal artificial nephron (mini-RAD). Phase II of the Quantum Project will involve scale-up of the mini-RAD, optimization of volume homeostasis strategies, testing of metabolic balance, and development of packaging and electronics. The various components will be integrated into an implantable RAD for demonstration to establish overall feasibility in an animal model. If successful, a FDA IND approval will be sought. After approval is received, the Quantum Project will terminate with a "first-in-human" demonstration of the miniaturized implantable RAD in an ESRD patient.